Role of early life gut microbiota in colonisation resistance development

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Our bodies are home to complex microbial communities, termed the microbiota, yet when we are born we are completely sterile. Soon after birth we become colonised by these beneficial bacteria, which shape our immune defence and efficiently limit infection by gut pathogens in a process known as colonisation resistance. However, disturbances in early colonisation events, such as caesarian sections (C-sections) and antibiotic exposure, can lead to increased susceptibility to pathogens, as well as allergic, and chronic inflammatory diseases in later life. Currently, our knowledge of the contribution of specific bacterial species during early life development, and how microbiota disturbances increase susceptibility to gut infection is incomplete. This Wellcome Trust New Investigator Award is focused on one of the major early life bacterial groups, bifidobacteria. The aim is to understand how (i) these pioneer bifidobacteria colonise the gut and (ii) subsequently modulate critical colonisation resistance, and to understand how (iii) early life antibiotic-induced disturbances alter this microbial community, ultimately leading to a breakdown in pathogen protection. Another key goal is to (iv) identify bifidobacterial communities that can restore a disturbed early life microbiota back into one able to control gut infection. A combination of state-of-the-art high-throughput sequencing technologies and subsequent bioinformatic analysis (16s rRNA, whole genome sequencing, RNASeq and metagenomics) and microbial culturing techniques will be used to investigate the early life microbiota, and in parallel, functional studies employing and developing innovative in vitro and germ-free SPF in vivo models will be performed to analyse the early life microbiota-host interaction.

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